Highlights of AAIC 2023
Authors: Philippa K Harris
Journal: The Lancet Healthy Longevity (2023)

Donanemab dominated the Alzheimer's Association International Conference in Amsterdam, the Netherlands (July 16–20). The results of the TRAILBLAZER-ALZ 2 phase 3 trial comparing donanemab with placebo were presented at an eagerly awaited session. Trial participants, categorised as having either low and medium tau or high tau, were randomly assigned to either donanemab or placebo given intravenously every 4 weeks for 72 weeks. The primary outcome was change in integrated Alzheimer Disease Rating Scale (iADRS) score, an integrated assessment of cognition and daily function, from baseline to 76 weeks in the low and medium tau population or combined low, medium, and high tau population versus placebo. The difference between the least-squares mean change in iARDS score was 3·25 (95% CI 1·88–4·62; p<0·001) in the low and medium tau group and 2·92 (1·51–4·33; p<0·001) in the combined donanemab groups compared with placebo. The positive results for donanemab were interpreted as conferring a 4·5-month delay in clinical decline in participants during the trial. However, adverse events, such as amyloid-related imaging abnormalities, headaches, infusion-related reactions, and superficial siderosis of the CNS were more frequent in the donanemab group. In addition, three deaths in the donanemab group and one in the placebo group were considered treatment-related. Despite progress in drug development, there was a lot of interest in non-pharmacological interventions to reduce the risk of developing Alzheimer's disease. The ACHIEVE trial, presented by Frank Lin and Josef Coresh (Johns Hopkins University, Baltimore, MD, USA), was a randomised trial of adults aged 70–84 years with untreated hearing loss but without substantial cognitive impairment. Participants were randomly assigned to a hearing intervention (audiological counselling and provision of hearing aids) or control intervention (health education). The primary endpoint was 3-year change in a global cognition standardised factor score from a comprehensive neurocognitive battery and did not differ between groups. However, in a subgroup of participants at increased risk of cognitive decline, a significant difference in the effect of the intervention on 3-year cognitive change was seen (pinteraction=0·010). Davangere P Devanand (Columbia University Medical Center, New York, NY, USA) discussed the results of the CogTraining trial, which compared the cognitive effects of random assignment to web-based computerised cognitive training versus crosswords. The primary outcome was change from baseline in the 11-item Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) score. In mixed model analysis, the ADAS-Cog score worsened for those playing computer games but improved with crosswords (p=0·04). A more personalised approach was presented by Kristine Yaffe (University of California, San Francisco, CA, USA) with the Systematic Multi-domain Alzheimer's Risk Reduction Trial (SMARRT). Participants in the intervention group chose between one and three Alzheimer's disease risk factors to work on and designed a personalised programme with help from a health coach. Participants in the control group received health education. Modest improvements in cognition, as measured by a composite score incorporating a number of cognitive tests, were seen in both groups, but the improvement in the intervention group was 80% greater than in the control group. Eric Lenze (Washington University School of Medicine, St Louis, MO, USA) discussed results from the Mindfulness, Education, and Exercise (MEDEX) trial, which ran for 18 months. The trial comprised four groups of mindfulness-based stress reduction, intensity-based multicomponent exercise, a combination of mindfulness and exercise or health education. Participants in the mindfulness-based stress reduction arm received group-based sessions and aimed to meditate for 60 min per day for the duration of the trial. Participants in the exercise group underwent an intensity-based multicomponent exercise programme with supervised group classes and aimed to exercise for 300 min per week for the duration of the trial. The combination group incorporated both interventions and the health education group received group-based classes. The primary outcome was memory and cognitive control and no significant difference was seen between the two components (ie, mindfulness or exercise). Analysis of the results suggested this was a negative rather than a failed trial as adherence across the groups was high and participants in the exercise group showed physical improvement. For more on the Alzheimer's Association International Conference see https://aaic.alz.org For more on the Alzheimer's Association International Conference see https://aaic.alz.org